Phase II year
2010
(last award dollars: 2011)
Phase II Amount
$1,388,920
The goal of this study is to develop a novel electrochemical S-nitrosothiol (RSNO) sensing system with an optimized detection limit and to finalize the specifications required to build a practical RSNO tool for clinical diagnostic applications. RSNO's are a primary carrier and reservoir of NO in vivo and are a potential pre-symptom marker for hypertensive disorders, endothelial dysfunction, cardiovascular risk and inflammation. However, the clinical significance of endogenous RSNO levels cannot be fully realized as a vascular diagnostic tool or biomarker without a quick and convenient assay for RSNO's. Compared to existing RSNO assay techniques, the proposed electrochemical RSNO sensor is highly sensitive and selective, is capable of rapidly measuring RSNO's in blood without separation or pretreatments and is suitable for simple and robust point-of-care use as a clinical diagnostic. A novel catalytic membrane will be prepared by covalently modifying cellulose dialysis membranes with selenocystamine to enhance the sensitivity of the RSNO sensor. The design parameters, including appropriate blood dilution ratios, light protection, temperature control, sensor/reagent stability and the tolerance to varying levels of blood components (e.g. hematocrit/hemoglobin) will be determined in Phase I and will serve as the criteria to build and validate the prototype point-of-care RSNO assay that will be assessed as a biomarker for pulmonary arterial hypertension (PAH) in Phase II.
Public Health Relevance: The goal in this grant is to develop a novel electrochemical S-nitrosothiol (RSNO) sensor with enhanced limit of detection, and to determine the specifications to use this RSNO sensor as the detector to build a practical RSNO analyzer for clinical diagnostic applications, first for trial in pulmonary arterial hypertension (PAH). Currently there is no quick and convenient technique to measure endogenous RSNO concentrations reliably.
Public Health Relevance Statement: The goal in this grant is to develop a novel electrochemical S-nitrosothiol (RSNO) sensor with enhanced limit of detection, and to determine the specifications to use this RSNO sensor as the detector to build a practical RSNO analyzer for clinical diagnostic applications, first for trial in pulmonary arterial hypertension (PAH). Currently there is no quick and convenient technique to measure endogenous RSNO concentrations reliably.
NIH Spending Category: Bioengineering; Biotechnology; Cardiovascular; Clinical Research; Clinical Trials; Heart Disease
Project Terms: Address; Affect; alpha-Cellulose; Assay; Bioassay; Bioavailability; bioavailability of drug; Biologic Assays; Biologic Availability; Biological Assay; Biological Availability; biomarker; Blood; Blood Glucose; Blood Plasma; Blood Sample; Blood specimen; Blood Sugar; Blood Vessels; BNP Gene Product; BNP-32; Brain natriuretic peptide; Brain Natriuretic Peptide-32; Calibration; Cardiac Catheterization Procedures; Cardiovascular Diseases; cardiovascular disorder; cardiovascular risk; cardiovascular risk factor; Catheterization, Cardiac; Cellulose; Cessation of life; Characteristics; Classification; Clinic; Clinical; clinical data repository; clinical data warehouse; clinical Diagnosis; Clinical Evaluation; clinical investigation; Clinical Research; clinical significance; Clinical Study; clinical test; Clinical Testing; Clinical Trials; Clinical Trials, Unspecified; clinically significant; Collection; comparison group; Data Banks; Data Bases; data repository; Databank, Electronic; Databanks; Database, Electronic; Databases; Death; design; designing; Detection; detector; Devices; Diagnosis; Diagnostic; Dialysis; Dialysis procedure; dialysis therapy; Disease; Disease Progression; disease/disorder; Disorder; drug/agent; Drugs; Dysfunction; Echocardiogram; Echocardiography; Electrodes; Endogenous Nitrate Vasodilator; endothelial cell derived relaxing factor; Endothelium-Derived Relaxing Factor; Equipment and supply inventories; Erythrocyte Volume, Packed; Ethics Committees, Research; Exhalation; Exhaling; Expiration, Respiratory; Family; Fingers; Functional disorder; glucose sensor; Goals; Grant; Hct; Heart; Heart Catheterization; Heart Catheterization Pocedure; heart sonography; Hematocrit; Hematocrit procedure; hemodynamics; Hemoglobin; HOSP; Hospitalization; improved; in vivo; Inflammation; INFLM; Insertion of catheter into heart chamber; Institutional Review Boards; Intravenous; Inventory; IRBs; language translation; Learning; Light; Lung; Marketing; Measurement; Measures; Medication; Membrane; membrane structure; Methods and Techniques; Methods, Other; Microfluidic; Microfluidics; Monitor; Mononitrogen Monoxide; Natriuretic factor, brain; Natriuretic Factor-32; Nesiritide; New York; Nitrates; Nitric Oxide; Nitric Oxide, Endothelium-Derived; Nitrites; Nitrogen Monoxide; Nitrogen oxide; Nitrogen Protoxide; novel; O element; O2 element; Oxygen; Packed Red-Cell Volume; Pathology; pathophysiology; Patients; Performance; Peripheral; Pharmaceutic Preparations; Pharmaceutical Preparations; Phase; Photoradiation; Physiologic; Physiologic Availability; Physiological; Physiopathology; Plasma; point of care; point-of-care diagnostics; Polyanhydroglucuronic Acid; Preparation; Pressure; pressure; Pressure- physical agent; Prevalence; Printing; Procedures; prototype; public health relevance; pulmonary; pulmonary arterial hypertension; quality assurance; Reagent; Registries; relational database; Reproducibility; Research; research clinical testing; Research Ethics Committees; Respiratory System, Lung; response; Reticuloendothelial System, Blood; Reticuloendothelial System, Serum, Plasma; Sampling; sensor; Serum, Plasma; Severities; sound measurement; Staging; Symptoms; System; System, LOINC Axis 4; Systematics; Techniques; Temperature; Testing; Therapeutic; tool; Translating; Translatings; transplant; Transplantation; Transthoracic Echocardiography; Treatment Failure; treatment response; Type-B Natriuretic Peptide; Validation; vascular; Veins; Venous; Walking
